Table 1.
Enteric pathogens and the inflammasomes: activation and inhibition
| Pathogen | Inflammasome | Virulence factor | Effect | References |
|---|---|---|---|---|
| A/E pathogens | CASP4/Casp11 | LPS (T3SS‐independent) (EPEC/EHEC) | Activator | (Knodler et al., 2014; Vanaja et al., 2016; Goddard et al., 2019) |
| CASP4 → NLRP3 | Stx (EHEC) | (Lee et al., 2016; Platnich et al., 2018) | ||
| Tir and LPS (T3SS‐dependent) (EPEC) | (Goddard et al., 2019) | |||
| NLRP3 | Haemolysin EhxA (EHEC) | (Zhang et al., 2012; Cheng et al., 2015) | ||
| Nlrp3 | RNA:DNA (EHEC) | (Vanaja et al., 2014) | ||
| Naip2‐Nlrc4 | EscI (T3SS rod; EPEC/EHEC), EprJ (ETT2 rod; EHEC) | (Miao, Mao, et al., 2010; Zhao et al., 2011; Wu et al., 2019) | ||
| NAIP‐NLRC4 OR Naip1‐Nlrc4 | EprI (ETT2 needle; EHEC) | (Yang et al., 2013; Zhao et al., 2016; Wu et al., 2019) | ||
| NLRP3 | NleA/EspI (EPEC) | Inhibitor | (Yen et al., 2015) | |
| CASP4/Casp11 | NleF (EPEC) | (Blasche et al., 2013; Pallett et al., 2017; Pollock et al., 2017) | ||
| Salmonella Typhimurium | NAIP‐NLRC4 OR Naip5/6‐Nlrc4 | Flagellin | Activator | (Broz, Newton, et al., 2010; Miao, Leaf, et al., 2010; Kofoed & Vance, 2011; Zhao et al., 2011; Franchi et al., 2012; Kortmann et al., 2015; Reyes Ruiz et al., 2017) |
| NAIP‐NLRC4 OR Naip2‐Nlrc4 | PrgJ (inner SPI‐1 T3SS rod) | (Kofoed & Vance, 2011; Zhao et al., 2011; Franchi et al., 2012; Tenthorey, Kofoed, Daugherty, Malik, & Vance, 2014; Reyes Ruiz et al., 2017) | ||
| NAIP‐NLRC4 OR Naip1‐Nlrc4 | PrgI (SPI‐1 T3SS needle) | (Zhao et al., 2011; Yang et al., 2013) | ||
| CASP4/Casp11 → NLRP3/Nlrp3 | LPS | (Shenoy et al., 2012; Meunier et al., 2014; Fisch et al., 2019) | ||
| CASP4/Casp11 | LPS | (Knodler et al., 2010; Broz et al., 2012; Knodler et al., 2014) | ||
| Nlrp3 | Curli fibres | (Rapsinski et al., 2015) | ||
| ? (↓NADH, ↑mitoROS)* | (Sanman et al., 2016) | |||
| Nlrp3?* | SlrP | Inhibitor | (Rao et al., 2017) | |
| Casp11 → Nlrp3 | Aconitase | (Wynosky‐Dolfi et al., 2014) | ||
| Shigella | CASP4/Casp11 | LPS | Activator | (Kobayashi et al., 2013; Shi et al., 2014; Watson et al., 2019) |
| Naip2‐Nlrc4 | MxiI (T3SS rod) | (Miao, Mao, et al., 2010; Yang et al., 2013; Suzuki, Franchi, et al., 2014; Zhao et al., 2016) | ||
| Naip‐NLRC4 OR Naip1‐Nlrc4 | MxiH (T3SS needle) | (Yang et al., 2013; Zhao et al., 2016) | ||
| NLRC4/Nlrc4? | IpaB | (Senerovic et al., 2012) | ||
| NLRP3/Nlrp3 & NLRC4/Nlrc4 | IpaH7.8 | (Suzuki, Mimuro, et al., 2014; Suzuki et al., 2018) | ||
| Nlrp1b | IpaH7.8 | (Neiman‐Zenevich et al., 2017; Sandstrom et al., 2019) | ||
| CASP4 | OspC3 | Inhibitor | (Kobayashi et al., 2013) | |
| Listeria monocytogenes | NLRP3/Nlrp3 | Listeriolysin (LLO) | Activator | (Zwaferink, Stockinger, Hazemi, Lemmens‐Gruber, & Decker, 2008; Meixenberger et al., 2010; Sauer et al., 2011; Eldridge et al., 2017) |
| Nlrp3 | p60 | (Schmidt & Lenz, 2012) | ||
| RNA | (Kanneganti et al., 2006) | |||
| Aim2 | dsDNA | (Kim et al., 2010; Rathinam et al., 2010; Tsuchiya et al., 2010; Warren et al., 2010; Wu et al., 2010) | ||
| Naip‐Nlrc4 | Flagellin | (Warren, Mao, Rodriguez, Miao, & Aderem, 2008; Sauer et al., 2010; Tsuchiya et al., 2010; Warren et al., 2010) | ||
| Nlrp6‐Casp4 | Lipoteichoic acid (LTA) | (Meixenberger et al., 2010; Hara et al., 2018) | ||
| CASP4 | ?* | (Hara et al., 2018) | ||
| Nlrp1b | Host cell energy stress?* | (Neiman‐Zenevich et al., 2017) | ||
| Yersinia | Nlrc4?* (in vivo) | YopB, YopD (Yps) | Activator | (Brodsky et al., 2010) |
| Nlrp3 | YopB, YopD (Yps) | (Brodsky et al., 2010; Zwack et al., 2015) | ||
| CASP4/Casp11 | LPS (Yps) | (Casson et al., 2013; Casson et al., 2015) | ||
| Rip1‐Casp8‐Casp1 | YopJ (Yps) | (Philip et al., 2014; Weng et al., 2014) | ||
| Pyrin | YopE, YopT (Yps) | (Chung et al., 2016; Ratner et al., 2016) | ||
| Naip5‐Nlrc4 | Flagellin (Ye) | (Matusiak et al., 2015) | ||
| Nlrp3 | YopK (Yps) | Inhibitor | (Brodsky et al., 2010, Zwack et al., 2015) | |
| Pyrin/ Casp1 | YopM (Yps) | (LaRock & Cookson, 2012; Chung et al., 2014; Chung et al., 2016; Ratner et al., 2016) | ||
| NLRP3/Nlrp3 | YopH, YopE (Ye) | (Schotte et al., 2004; Thinwa et al., 2014) |
Notes: Bacterial components and infection‐mediated alterations of host cells that lead to inflammasome activation are shaded in orange; inflammasome inhibitors are shown shaded in blue. Indirect inhibitors of NLRP3, for example via inhibition of NF‐κB signalling, are not featured in the table (refer to text). H. pylori‐encoded direct activators/inhibitors of inflammasome activation not well defined, and thus the pathogen is not included. When the human inflammasome genes have been involved, these are shown in uppercase (e.g. NLRP3); mouse genes are shown in lowercase except the first letter (e.g. Nlrp3). * indicates when the study does not define which inflammasome is involved or what the bacterial activating signal/factor is.
Abbreviations: mitoROS, mitochondrial reactive oxygen species; Ye, Yersinia enterocolitica; Yps, Yersinia pseudotuberculosis.